Clinical Rheumatology

, Volume 30, Issue 3, pp 409–413 | Cite as

Interleukin-6 promoter polymorphism −174 G/C is associated with nephritis in Portuguese Caucasian systemic lupus erythematosus patients

  • Maria José Santos
  • Diana Fernandes
  • Susana Capela
  • Jose Canas da Silva
  • João Eurico Fonseca
Brief Report


Interleukin-6 (IL-6) is a multifunctional cytokine with an important pathophysiological role in systemic lupus erythematosus (SLE). The polymorphism of the IL-6 gene promoter at position −174, which appears to influence the production of this cytokine, has been associated with susceptibility to some rheumatic diseases. The aim of this study is to investigate whether the IL-6 −174 G/C polymorphism associates with lupus susceptibility or affects disease characteristics in Portuguese patients with SLE. The association between −174 G/C and lupus diagnosis was studied in 115 adult SLE patients (95.7% females) and 152 healthy controls (94.7% females), all Caucasians. There were no significant differences in genotype or allele frequency between patients and controls. The −174 C/C genotype was independently associated with renal disease and the C allele with the presence of irreversible damage. The IL-6 gene promoter polymorphism at position −174 does not contribute to SLE susceptibility in Portuguese Caucasian patients but may predispose to specific manifestations of the disease.


Interleukin-6 Portuguese Caucasian Systemic lupus erythematosus 



This work was supported by a grant from Fundação para a Ciência e a Tecnologia, Portugal (PIC/IC/82920/2007) and by an unrestricted grant from Wyeth Portugal.




  1. 1.
    Fonseca JE, Santos MJ, Canhão H, Choy E (2009) Interleukin-6 as a key player in systemic inflammation and joint destruction. Autoimmun Rev 8:538–542PubMedCrossRefGoogle Scholar
  2. 2.
    Kiberd BA (1993) Interleukin-6 receptor blockage ameliorates murine lupus nephritis. J Am Soc Nephrol 4:58–61PubMedGoogle Scholar
  3. 3.
    Cash H, Relle M, Menke J, Brochhausen C, Jones SA, Topley N, Galle PR, Schwarting A (2010) Interleukin 6 (IL-6) deficiency delays lupus nephritis in MRL-Fas lpr mice: the IL-6 pathway as a new therapeutic target in treatment of autoimmune kidney disease in systemic lupus erythematosus. J Rheumatol 37:60–70PubMedCrossRefGoogle Scholar
  4. 4.
    Chun HY, Chung JW, Kim HA, Yun JM, Jeon JY, Ye YM et al (2007) Cytokine IL-6 and IL-10 as biomarkers in systemic lupus erythematosus. J Clin Immunol 27:461–466PubMedCrossRefGoogle Scholar
  5. 5.
    Mellor-Pita S, Citores MJ, Castejon R, Yebra-Bango M, Tutor-Ureta P, Rosado S et al (2009) Monocytes and T lymphocytes contribute to a predominance of interleukin 6 and interleukin 10 in systemic lupus erythematosus. Cytometry B Clin Cytom 76B:261–270CrossRefGoogle Scholar
  6. 6.
    Nürnberg W, Haas N, Schadendorf D, Czarnetzki BM (1995) Interleukin-6 expression in the skin of patients with lupus erythematosus. Exp Dermatol 4:52–57PubMedCrossRefGoogle Scholar
  7. 7.
    Illei GG, Shirota Y, Yarboro CH, Daruwalla J, Tackey E, Takada K et al (2010) Tocilizumab in systemic lupus erythematosus: data on safety, preliminary efficacy, and impact on circulating plasma cells from an open-label phase I dosage-escalation study. Arthritis Rheum 62:542–552PubMedCrossRefGoogle Scholar
  8. 8.
    Fishman D, Faulds G, Jeffery R, Mohamed-Ali V, Yudkin JS, Humphries S et al (1998) The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest 102:1369–1376PubMedCrossRefGoogle Scholar
  9. 9.
    Hulkkonen J, Pertovaara M, Antonen J, Pasternack A, Hurme M (2001) Elevated interleukin-6 plasma levels are regulated by the promoter region polymorphism of the IL6 gene in primary Sjögren’s syndrome and correlate with the clinical manifestations of the disease. Rheumatology (Oxford) 40:656–661CrossRefGoogle Scholar
  10. 10.
    Vickers MA, Green FR, Terry C, Mayosi BM, Julier C, Lathrop M et al (2002) Genotype at a promoter polymorphism of the interleukin-6 gene is associated with baseline levels of plasma C-reactive protein. Cardiovasc Res 53:1029–1034PubMedCrossRefGoogle Scholar
  11. 11.
    Sie MP, Sayed-Tabatabaei FA, Oei HH, Uitterlinden AG, Pols HA, Hofman A et al (2006) Interleukin 6–174 G/C promoter polymorphism and risk of coronary heart disease: results from the Rotterdam Study and a meta-analysis. Arterioscler Thromb Vasc Biol 26:212–217PubMedCrossRefGoogle Scholar
  12. 12.
    Hrycek A, Siekiera U, Cieślik P, Szkróbka W (2005) HLA-DRB1 and -DQB1 alleles and gene polymorphisms of selected cytokines in systemic lupus erythematosus. Rheumatol Int 26:1–6PubMedCrossRefGoogle Scholar
  13. 13.
    Chua KH, Kee BP, Tan SY, Lian LH (2009) Interleukin-6 promoter polymorphisms (−174 G/C) in Malaysian patients with systemic lupus erythematosus. Braz J Med Biol Res 42:551–555PubMedCrossRefGoogle Scholar
  14. 14.
    Linker-Israeli M, Wallace DJ, Prehn J, Michael D, Honda M, Taylor KD et al (1999) Association of IL-6 gene alleles with systemic lupus erythematosus (SLE) and with elevated IL-6 expression. Genes Immun 1:45–52PubMedCrossRefGoogle Scholar
  15. 15.
    Schotte H, Schlüter B, Rust S, Assmann G, Domschke W, Gaubitz M (2001) Interleukin-6 promoter polymorphism (−174 G/C) in Caucasian German patients with systemic lupus erythematosus. Rheumatology (Oxford) 40:393–400CrossRefGoogle Scholar
  16. 16.
    Guarnizo-Zuccardi P, Lopez Y, Giraldo M, Garcia N, Rodriguez L, Ramirez L et al (2007) Cytokine gene polymorphisms in Colombian patients with systemic lupus erythematosus. Tissue Antigens 70:376–382PubMedCrossRefGoogle Scholar
  17. 17.
    Godarzi EM, Sarvestani EK, Aflaki E, Amirghofran Z. Interleukin-6 gene polymorphism in Iranian patients with systemic lupus erythematosus. Clin Rheumatol 2010 Apr 11. [Epub ahead of print].Google Scholar
  18. 18.
    Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725PubMedCrossRefGoogle Scholar
  19. 19.
    Gladman DD, Ibañez D, Urowitz MB (2002) Systemic lupus erythematosus disease activity index 2000. J Rheumatol 29:288–291PubMedGoogle Scholar
  20. 20.
    Gladman D, Ginzler E, Goldsmith C, Fortin P, Liang M, Urowitz M et al (1996) The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for systemic lupus erythematosus. Arthritis Rheum 39:363–369PubMedCrossRefGoogle Scholar
  21. 21.
    Santos MJ, Capela S, Figueira R, Nero P, Matos AA, Silva C et al (2007) Characterization of a Portuguese population with systemic lupus erytematosus. Acta Reumatol Port 32:153–161PubMedGoogle Scholar
  22. 22.
    Herrera-Esparza R, Barbosa-Cisneros O, Villalobos-Hurtado R, Avalos-Díaz E (1998) Renal expression of IL-6 and TNFalpha genes in lupus nephritis. Lupus 7:154–158PubMedCrossRefGoogle Scholar
  23. 23.
    Tsai CY, Wu TH, Yu CL, Lu JY (2000) Tsai YY.Increased excretions of beta2-microglobulin, IL-6, and IL-8 and decreased excretion of Tamm–Horsfall glycoprotein in urine of patients with active lupus nephritis. Nephron 85:207–214PubMedCrossRefGoogle Scholar
  24. 24.
    Brull DJ, Montgomery HE, Sanders J et al (2001) Interleukin-6 gene −174 G>C and −572 G>C promoter polymorphisms are strong predictors of plasma interleukin-6 levels after coronary artery bypass surgery. Arterioscler Thromb Vasc Biol 21:1458–1463PubMedCrossRefGoogle Scholar
  25. 25.
    Terry CF, Loukaci V, Green FR (2000) Cooperative influence of genetic polymorphisms on interleukin 6 transcriptional regulation. J Biol Chem 275:18138–18144PubMedCrossRefGoogle Scholar

Copyright information

© Clinical Rheumatology 2010

Authors and Affiliations

  • Maria José Santos
    • 1
    • 2
  • Diana Fernandes
    • 1
  • Susana Capela
    • 3
  • Jose Canas da Silva
    • 2
  • João Eurico Fonseca
    • 1
    • 3
  1. 1.Rheumatology Research Unit, Instituto de Medicina MolecularFaculdade de Medicina da Universidade de LisboaLisbonPortugal
  2. 2.Serviço de ReumatologiaHospital Garcia de OrtaAlmadaPortugal
  3. 3.Rheumatology and Bone Metabolic DiseasesHospital Santa MariaLisbonPortugal

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